PLX131802

GSE91078: Deletion of Gas2l3 in mice leads to specific defects in cardiomyocyte cytokinesis during development

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Mammalian cardiomyocytes lose the ability to proliferate shortly after birth. This accounts for the limited regeneration capacity of the mammalian heart. A characteristic feature of growth arrested cardiomyocytes is binucleation, but the molecular mechanisms are not well understood. In rodents, binucleation of cardiomyocytes starts after birth and occurs through incomplete cytokinesis. Here we demonstrate an important and unexpected role of GAS2L3, a recently identified actin and tubulin binding protein, for cardiomyocyte cytokinesis during heart development in mice. Mice deficient in GAS2L3 die shortly after birth due to dilated cardiomyopathy. Cardiomyocyte-specific deletion of GAS2L3 confirmed that the phenotype resulted from the loss of GAS2L3 in cardiomyocytes. We show that a deficiency in GAS2L3 leads to a strong reduction in cardiomyocyte numbers due to reduced proliferation. In addition, the loss of Gas2l3 resulted in premature binucleation of cardiomyocytes and in induction of a p53-transcriptional program including the cell cycle inhibitor p21. Collectively, these data identify an important role for GAS2L3 in cardiomyocyte cytokinesis during development. SOURCE: Stefan Gaubatz (stefan.gaubatz@biozentrum.uni-wuerzburg.de) - Gaubatz University of Wuerzburg